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“Drug candidates that previously would not have been considered feasible — they’re now on the table. Hybrid synthesis is opening the door to peptide drugs you’re going to need in larger quantities.”
Brian Gregg, CEO of AmbioPharm, has spent his career in the peptide contract development and manufacturing organization (CDMO) industry — including early work on exenatide, the first approved GLP-1 receptor agonist for Type 2 diabetes. Today, he leads AmbioPharm through a period of significant strategic expansion, anchored by a differentiated capability: hybrid peptide synthesis.
In this episode of the PharmaSource podcast, Brian explains why hybrid synthesis is rapidly becoming the defining manufacturing advantage in the GLP-1 era, how AmbioPharm is building mirror-image facilities in Shanghai and South Carolina to de-risk customer supply chains, and why the company’s dual-continent footprint is an asset.
What Is Hybrid Synthesis — and Why Does It Matter?
Traditional peptide manufacturing relies on linear solid-phase peptide synthesis (SPPS), in which amino acids are coupled one at a time onto an insoluble resin. For short sequences, this approach works well. But for long peptides, such as GLP-1 agonists running to around 39 amino acids, the method becomes problematic. As chains grow longer, the peptide begins to fold back on itself, making it difficult to access the free amine needed for each coupling step. The result is a complex impurity profile, reduced yield, longer timelines, and a significantly harder purification burden.
“You end up getting very complex impurity profiles with missing amino acids or even truncated sequences — shortened sequences that reduce yield and make purification extremely difficult.”
AmbioPharm’s hybrid approach addresses this. Rather than building a peptide in one linear sequence, the team breaks it into multiple shorter fragments — typically three to five — each synthesized individually using SPPS. These fragments are then joined together through liquid-phase peptide synthesis (LPPS). The result is a cleaner crude peptide with a simpler impurity profile, easier purification, higher yield, long-term cost savings, reduced lead times, improved manufacturing risk-mitigation, and — critically — the ability to manufacture fragments in parallel, which compresses overall timelines.
The commercial implications are significant. Brian notes that manufacturers can deliver larger volumes more quickly at a lower cost of goods (COGS), making the economics viable for drug programs that would previously have been deprioritized or killed.
“It’s opening the door for drug development companies to put resources into developing peptides that, not long ago, would not have been considered practical or viable.”
A Differentiated Go-to-Market in a Crowded CDMO Landscape
When Brian joined AmbioPharm following the company’s spin-out of its generic peptide business, he identified a clear strategic gap. The broader peptide CDMO industry had spent the prior decade and a half making substantial investments in traditional linear SPPS, both in equipment and in institutional knowledge, which shaped the approaches used for peptide manufacturing.
AmbioPharm’s opportunity, as Brian saw it, was to move in the opposite direction: to build a reputation as the go-to CDMO specifically for hybrid synthesis, particularly for late-phase development and commercial manufacturing of innovative drugs requiring large volumes.
“The peptide CDMO industry, in general, is very motivated to steer customers to linear SPPS. For us, it was really clear that the opportunity was to focus on hybrid fragment-based approaches as a clear differentiator.”
That positioning has gained traction, partly because of high-profile validation from within the industry itself. Eli Lilly’s publicized success with hybrid fragment-based approaches for its GLP-1 portfolio has raised awareness among drug developers, and those companies are now actively seeking CDMOs with demonstrable hybrid capabilities.
AmbioPharm’s ability to demonstrate proof of concept and then rapidly progress from pilot to manufacturing scale has allowed it to build a track record with innovative drug companies. Brian describes the company as increasingly recognized in the market as the specialist CDMO for hybrid synthesis.
Sustainability: A 3-4x Reduction in Process Mass Intensity
Beyond speed and yield, hybrid synthesis carries a sustainability advantage that is becoming increasingly important to large pharmaceutical customers. The metric at the center of this discussion is Process Mass Intensity (PMI) — a measure of manufacturing efficiency calculated by dividing the total mass of all raw material inputs (solvents, reagents, amino acid derivatives) by the mass of the final API output.
For a 39-mer GLP-1 peptide manufactured by traditional linear SPPS, PMI typically falls in the range of 20,000 to 30,000, meaning an enormous quantity of input materials is required to produce a small quantity of finished product. AmbioPharm’s hybrid approach delivers a three to fourfold reduction in PMI for the same molecule.
“A three to fourfold reduction in PMI is a really meaningful reduction compared to the linear SPPS approach — and it significantly improves sustainability, which is particularly attractive to large global pharma companies trying to achieve their environmental goals.”
As ESG commitments intensify across the pharmaceutical sector, this capability is moving from a differentiator to a baseline expectation for preferred CDMO partners, particularly among large multinational customers with publicly committed carbon-reduction targets.
Mirror Facilities on Two Continents
AmbioPharm recently completed a major manufacturing expansion in Shanghai. A state-of-the-art facility with full SPPS, LPPS, and hybrid synthesis capabilities, built to replace an aging site and to meet growing near-term customer demand. The company is now replicating that exact design by adding 68,000 square feet of space in South Carolina, with synthesis capabilities expected to be fully operational by Q4 2027.
The strategic logic is straightforward: customers with commercial-scale programs need supply chain optionality. Having two facilities with identical technical capabilities and processes means that tech transfer between them is, in principle, seamless, reducing the complexity and risk of shifting production from one geography to another. It allows programs to move efficiently between sites while maintaining consistent quality standards and helping ensure therapies can reach patients without disruption.
“What this replicated capability in South Carolina is able to provide to our customers is the ability to mitigate supply chain risk — and to have supply nodes that can serve the US, European, and increasingly important Chinese markets.”
The decision to build in Shanghai first, rather than immediately in South Carolina, was based on cost and speed. An existing building was already earmarked for the expansion, construction costs were lower, and — as Brian describes it — “China speed” allowed the company to meet immediate customer capacity needs far more quickly than a greenfield US build would have permitted.
Now that the Shanghai facility is complete, Brian describes the South Carolina investment as a straightforward decision. AmbioPharm spoke with its customers about their growth, their challenges, and the pressures they face to move promising therapies forward without delay. The investment positions AmbioPharm to support the rapidly growing pipeline of its customers. Based on long-range customer forecasts, AmbioPharm expects to reach full utilization of its new US capacity within three to four years of coming online — and anticipates further expansion within the following five years.
A Modular Build Approach
To accelerate the South Carolina timeline, AmbioPharm is using a prefabricated modular construction approach — with modules built in China, in close collaboration with the Shanghai engineering team, then shipped and assembled on-site in the US. This approach targets a two-year project completion timeline, compared to three or more years for a conventional stick-build. It positions AmbioPharm to rapidly add US commercial-scale capacity.
China as an Asset: Capturing Innovation at the Source
In an environment where China exposure is often framed as a risk factor, AmbioPharm takes a different view. AmbioPharm’s presence in both the US and China allows the company to support innovators globally while giving partners flexibility in where development and manufacturing activities take place. By some estimates, China now accounts for 20-30% of global drug development — second only to the US at approximately 40% — and that share is growing. The company’s Shanghai presence gives it direct access to this pool of innovation.
For Chinese drug innovators seeking to license or out-license their programs to US and European companies, having a CDMO with development and manufacturing capabilities in both China and the US offers a specific and commercially valuable advantage: rapid, seamless tech transfer that allows clinical development to proceed outside China without delays.
“We’ve already seen this play out. These innovators can make deals, license out their products, and then very quickly and seamlessly transfer manufacturing from China to the US — allowing them to proceed with clinical development activities outside of China. It’s a clear enhancement of their value story.”
For established global pharma customers, meanwhile, the dual-geography model offers something equally attractive: the ability to use both facilities as supply nodes serving different markets — including the growing Chinese market itself.
Beyond Obesity: The Expanding Peptide Drug Landscape
While GLP-1 drugs have captured global attention, peptide innovation is expanding rapidly across a growing range of therapeutic areas. GLP-1 pipelines continue to evolve, from pure GLP-1 agonists to dual and triple agonists, promising additional clinical benefits beyond weight loss. But Brian argues that the more significant shift is structural: the success of GLP-1s has fundamentally changed the industry’s risk calculus for peptide drug development.
Drug candidates that once might have been deprioritized because of manufacturing complexity or volume concerns are now being revisited. Beyond metabolic diseases, Brian sees growing development activity in oncology, endocrinology, autoimmune diseases, and arthritis — areas where peptide drugs are now being seriously evaluated by customers across AmbioPharm’s portfolio.
“The success of GLP-1s has really changed the paradigm about what can be a viable peptide drug. That boom in peptide drugs is going to continue well beyond obesity.”
As peptide innovation accelerates across therapeutic areas, scalable manufacturing will play an essential role in ensuring these therapies can reach patients reliably and at volumes required worldwide.